In order to prevent organ rejection, patients receiving liver transplants currently require life-long treatment with immune system suppressing medications to prevent the rejection of the transplanted liver. However, in patients infected with hepatitis C virus (HCV), these medications may increase the risk for HCV infection in the transplanted liver. The purpose of this study is to determine whether a slow withdrawal of immune system suppressing medications is safe and decreases the chance for HCV infection of the new liver transplant patients with HCV.

Condition	Intervention	Phase
Hepatitis C Hepatitis C, Chronic	Drug: Tacrolimus  Drug: Corticosteroids  Procedure: Immunosuppression withdrawal  Procedure: Liver Transplant	Phase II

Further Study Details: 

Primary Outcomes: Proportion of participants with progression of hepatitis C-related liver disease, defined as Stage 4 or higher fibrosis on the Ishak scale, in the 2 years following random assignment
Secondary Outcomes: Tolerance induction; laboratory tests indicative of successful withdrawal; hepatitis C immune response and graft injury; definition of rejection profiles from laboratory tests
Expected Total Enrollment:  157

Over 60% of liver transplants are done in patients who are infected with HCV. Following organ transplants, immunosuppressive medications are used to prevent the patient’s immune system from rejecting the transplanted organ. In general, these anti-rejection drugs are prescribed for the remainder of the transplant recipient’s life. However, in patients infected with HCV, these same medications are believed to be associated with a rapid reoccurrence of HCV, which can lead to failure of the transplanted liver, severe hepatitis, cirrhosis, and other serious conditions. This study will evaluate how safe it is to slowly withdraw anti-rejection medications without the rejection of the transplanted liver in patients with HCV-related liver failure receiving a liver transplant. The study will also determine if the risk for HCV infection in the transplanted liver decreases with this regimen in these patients.

Participants will undergo liver transplantation and receive immunosuppression medications consistent with current standard practices. This includes "induction immunosuppression" with 2 immunosuppressive drugs, tacrolimus and corticosteroids. Patients will be tapered off of corticosteroids in the first three months, but will continue tacrolimus maintenance immunosuppression for 1 year. Participants will be regularly monitored for reoccurrence of hepatitis and for evidence of allograft rejection. One year after transplantation, participants who meet certain criteria for immunosuppressive withdrawal will be randomly assigned to either the immunosuppression withdrawal group or the control group. Participants assigned to the drug withdrawal group will have their dose of tacrolimus tapered off over the course of 1 year. The control group will be maintained on normal levels of tacrolimus.

During and after the withdrawal phase, participants will be closely monitored for liver function, signs of rejection, levels of HCV in the blood and liver, and for the response of the immune system to the withdrawal of immunosuppression. Participants will be followed for a minimum of 1 year after the completion of withdrawal, possibly up to 4 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Hepatitis C infection with genotype 1, as demonstrated by presence of RNA genomes in serum
• Needs liver transplant
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• Previous transplant
• Multiorgan or split liver transplant
• Living donor transplant
• Donor liver from a donor positive for antibody against hepatitis B core antigen
• Donor liver from a donor positive for antibody against hepatitis C
• Donor liver from a non-heart-beating donor
• Liver failure due to autoimmune disease
• Fulminant liver failure
• Hepatitis B virus infection
• Stage III or higher hepatocellular cancer
• History of cancer. Patients with hepatocellular cancer, adequately treated in situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of skin are not excluded.
• Active systemic infection at the time of transplantation
• Clinically significant chronic renal disease
• Clinically significant cardiovascular or cerebrovascular disease
• HIV infected
• Pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00135694

Mary C. Shaw, RN, BBA      (215) 614-0528    mary.shaw@uphs.upenn.edu

Colorado
      University of Colorado, Denver,  Colorado,  80262,  United States
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States

Study chairs or principal investigators

Abraham Shaked, MD, PhD,  Principal Investigator,  University of Pennsylvania   

Study ID Numbers:  ITN030ST
Last Updated:  August 25, 2005
Record first received:  August 25, 2005
ClinicalTrials.gov Identifier:  NCT00135694
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-30